Cefepime

Cefepime

88040-23-7

Cefepime

CAS Registry Number: 88040-23-7

CAS Name: 1-[[(6R,7R)-7-[[(2Z)-(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium inner salt

Additional Names: 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium hydroxide inner salt 72-(Z)-2-(O-methyloxime); 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate

Manufacturers’ Codes: BMY-28142

Molecular Formula: C19H24N6O5S2

Molecular Weight: 480.56

Percent Composition: C 47.49%, H 5.03%, N 17.49%, O 16.65%, S 13.34%

Literature References: Semisynthetic, fourth generation cephalosporin antibiotic. Prepn: S. Aburaki et al.,DE3307550; eidem,US4406899 (both 1983 to Bristol-Myers); and antibacterial activity: T. Naito et al.,J. Antibiot.39, 1092 (1986). In vitro comparative antimicrobial spectrum: N. J. Khan et al.,Antimicrob. Agents Chemother.26, 585 (1984); and b-lactamase stability: H. C. Neu et al.,J. Antimicrob. Chemother.17, 441 (1986). HPLC determn in plasma and urine: R. H. Barbhaiya et al.,Antimicrob. Agents Chemother.31, 55 (1987). Clinical evaluations in infection: N. Clynes et al.,Diagn. Microbiol. Infect. Dis.12, 257 (1989); S. Oster et al.,Antimicrob. Agents Chemother.34, 954 (1990). Review of clinical pharmacokinetics: M. P. Okamoto et al.,Clin. Pharmacokinet.25, 88-102 (1993).

Properties: Colorless powder, mp 150° (dec). uv max (pH 7 phosphate buffer): 235, 257 nm (e 16700, 16100).

Melting point: mp 150° (dec)

Absorption maximum: uv max (pH 7 phosphate buffer): 235, 257 nm (e 16700, 16100)

Derivative Type: Sulfate

Molecular Formula: C19H24N6O5S2.H2SO4

Molecular Weight: 578.64

Percent Composition: C 39.44%, H 4.53%, N 14.52%, O 24.89%, S 16.62%

Properties: mp 210° (dec). uv max (pH 7 phosphate buffer): 236, 258 nm (e 17200, 16900).

Melting point: mp 210° (dec)

Absorption maximum: uv max (pH 7 phosphate buffer): 236, 258 nm (e 17200, 16900)

Derivative Type: Hydrochloride monohydrate

CAS Registry Number: 123171-59-5

CAS Name: 1-[[(6R,7R)-7-[[(2Z)-(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride monohydrochloride monohydrate

Additional Names: cefepime hydrochloride

Trademarks: Axepim (BMS); Cepimex (Mead Johnson); Maxipime (BMS)

Molecular Formula: C19H25ClN6O5S2.HCl.H2O

Molecular Weight: 571.50

Percent Composition: C 39.93%, H 4.94%, Cl 12.41%, N 14.71%, O 16.80%, S 11.22%

Therap-Cat: Antibacterial.

Keywords: Antibacterial (Antibiotics); ?Lactams; Cephalosporins.

FDA APPROVED 2/22/2024, To treat complicated urinary tract infections, Exblifep

• BMY 28142
• BMY-28142

Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents. A 2007 meta-analysis suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics.^[1] In response, the U.S. Food and Drug Administration (FDA) performed their own meta-analysis which found no mortality difference.^[2]

Cefepime was patented in 1982 by Bristol-Myers Squibb and approved for medical use in 1994.^[3] It is available as a generic drug and sold under a variety of trade names worldwide.^{[citation needed][4]}

It was removed from the World Health Organization’s List of Essential Medicines in 2019.^[5]

Medical use

Cefepime is usually reserved to treat moderate to severe nosocomial pneumonia, infections caused by multiple drug-resistant microorganisms (e.g. Pseudomonas aeruginosa) and empirical treatment of febrile neutropenia.^[6]

Cefepime has good activity against important pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, and multiple drug-resistant Streptococcus pneumoniae. A particular strength is its activity against Enterobacteriaceae. Whereas other cephalosporins are degraded by many plasmid– and chromosome-mediated beta-lactamases, cefepime is stable and is a front-line agent when infection with Enterobacteriaceae is known or suspected.^{[medical citation needed]}

Spectrum of bacterial susceptibility

Cefepime is a broad-spectrum cephalosporin antibiotic and has been used to treat bacteria responsible for causing pneumonia and infections of the skin and urinary tract. Some of these bacteria include Pseudomonas, Escherichia, and Streptococcus species. The following represents MIC susceptibility data for a few medically significant microorganisms:^[7]

• Escherichia coli: ≤0.007 – 128 μg/ml
• Pseudomonas aeruginosa: 0.06 – >256 μg/ml
• Streptococcus pneumoniae: ≤0.007 – >8 μg/ml

Chemistry

The combination of the syn-configuration of the methoxy imino moiety and the aminothiazole moiety confers extra stability to β-lactamase enzymes produced by many bacteria. The N–methyl pyrrolidine moiety increases penetration into Gram-negative bacteria. These factors increase the activity of cefepime against otherwise resistant organisms including Pseudomonas aeruginosa and Staphylococcus aureus.

Semisynthetic, fourth generation cephalosporin antibiotic. Prepn: S. Aburaki et al., DE 3307550; eidem, US 4406899 (both 1983 to Bristol-Myers); and antibacterial activity: T. Naito et al., J. Antibiot. 39, 1092 (1986).

Trade names

Following expiration of the Bristol-Myers Squibb patent,^[] cefepime became available as a generic and is now^] marketed by numerous companies worldwide under tradenames including Neopime (Neomed), Maxipime, Cepimax, Cepimex, and Axepim.

References

1. ^ Yahav D, Paul M, Fraser A, Sarid N, Leibovici L (May 2007). “Efficacy and safety of cefepime: a systematic review and meta-analysis”. The Lancet. Infectious Diseases. 7 (5): 338–348. doi:10.1016/S1473-3099(07)70109-3. PMID 17448937.
2. ^ “FDA Alert: Cefepime (marketed as Maxipime)”. Information for Healthcare Professionals. Food and Drug Administration. Archived from the original on 2 November 2017. Retrieved 2 August 2009.
3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 496. ISBN 9783527607495. Archived from the original on 19 June 2021. Retrieved 19 September 2020.
4. ^ “Cefepime (maxipime), large spectrum 4th generation cephalosporin, resistant to beta-lactamases]”.
5. ^ World Health Organization (2019). Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines. Geneva: World Health Organization. hdl:10665/325773. WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO.
6. ^ Chapman TM, Perry CM (2003). “Cefepime: a review of its use in the management of hospitalized patients with pneumonia”. American Journal of Respiratory Medicine. 2 (1): 75–107. doi:10.1007/bf03256641. PMID 14720024.
7. ^ “Cefepime Susceptibility and Concentration Range (μg/ml) Minimum Inhibitory Concentration (MIC) Data” (PDF). The Antimicrobial Index. toku-e.com. Archived from the original (PDF) on 1 November 2018.

External links

• “Cefepime”. Drug Information Portal. U.S. National Library of Medicine.

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